While pronounced species and strain differences are known to exist in the susceptibility of rodents to the carcinogenicity of 1,2-dimethylhydrazine, the underlying pharmacological and biochemical mechanisms are not known. Using sensitive high pressure liquid chromatographic methods that we have developed, we propose to study and compare the blood, urinary and tissue levels of 1,2-dimethylhydrazine, 1,1-dimethylhydrazine, monomethylhydrazine and hydrazine after the administration of various dose levels and at various times after administration. In the case of the methylated hydrazines, 14C label will also be used so that the levels of DNA methylation can be measured and correlated with the pharmacokinetics of the hydrazines. We expect that the differences in species and strain differences in susceptibility to 1,2-dimethylhydrazines will be reflected in a pattern of pharmacological parameters to which the other hydrazines may also conform. Such correlations will be tested by carcinogenicity bioassays. The information derived from these studies is expected to be significant in the eventual extrapolation of animal carcinogenicity, toxicity and metabolism data to man.